Is ABCD1 p.Leu173Pro (c.518T>C) pathogenic?

ABCD1 p.Leu173Pro (c.518T>C) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-01). AlphaMissense: likely pathogenic (0.8487); Absent from gnomAD v4.1.

How common is ABCD1 p.Leu173Pro (c.518T>C) in the general population?

ABCD1 p.Leu173Pro (c.518T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Leu173Pro (c.518T>C)?

AlphaMissense predicts likely pathogenic (score 0.8487) — an in-silico prediction, not a clinical call.

ABCD1 p.Leu173Pro

c.518T>C · rs2148389338 · VCV1176607

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8487	likely pathogenic ✓ concordant with ClinVar
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -13.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.21, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Leu173Pro
Coding: c.518T>C
MANE Select: NM_000033
dbSNP: rs2148389338
Type: single nucleotide variant
Location: chrX:153725784 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 173: an α-helix; the abc transmembrane type-1 domain; the 'interaction with pex19' region

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD1 c.1635-2A>G Pathogenic ★★ same type
ABCD1 c.1781-1G>C Pathogenic ★★ same type
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-1G>C Likely pathogenic ★★ same type
ABCD1 c.1866-2A>T Likely pathogenic ★★ same type
ABCD1 c.901-1G>A Pathogenic ★★ same type
ABCD1 c.901-5C>A Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcd1-p-leu173pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown